Neuropathy is a cause of significant disability in patients with Fabry disease, yet its diagnosis is difficult. In this study we compared the novel noninvasive techniques of corneal confocal microscopy (CCM) to quantify small-fiber pathology, and non-contact corneal aesthesiometry (NCCA) to quantify loss of corneal sensation, with established tests of neuropathy in patients with Fabry disease. Ten heterozygous females with Fabry disease not on enzyme replacement therapy (ERT), 6 heterozygous females, 6 hemizygous males on ERT, and 14 age-matched, healthy volunteers underwent detailed quantification of neuropathic symptoms, neurological deficits, neurophysiology, quantitative sensory testing (QST), NCCA, and CCM. All patients with Fabry disease had significant neuropathic symptoms and an elevated Mainz score. Peroneal nerve amplitude was reduced in all patients and vibration perception threshold was elevated in both male and female patients on ERT. Cold sensation (CS) threshold was significantly reduced in both male and female patients on ERT (P < 0.02), but warm sensation (WS) and heat-induced pain (HIP) were only significantly increased in males on ERT (P < 0.01). However, corneal sensation assessed with NCCA was significantly reduced in female (P < 0.02) and male (P < 0.04) patients on ERT compared with control subjects. According to CCM, corneal nerve fiber and branch density was significantly reduced in female (P < 0.03) and male (P < 0.02) patients on ERT compared with control subjects. Furthermore, the severity of neuropathic symptoms and the neurological component of the Mainz Severity Score Index correlated significantly with QST and CCM. This study shows that CCM and NCCA provide a novel means to detect early nerve fiber damage and dysfunction, respectively, in patients with Fabry disease.

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Two mechanisms of potential biologic antagonism of gentamicin in purulent sputum from patients with cystic fibrosis or bronchiectasis were studied: reduction of activity by ions and antibiotic binding. Antagonism by ions was assessed by examination of the activity of gentamicin against Pseudomonas aeruginosa in dialysates of serum or sputum in ion-depleted broth. The ionic content of the dialysates increased and reflected differences in the ion content of serum and sputum. Gentamicin had significantly less activity against P aeruginosa in sputum or serum dialysates than in ion-depleted broth alone. When gentamicin was mixed with serum or sputum before dialysis, the level of antipseudomonas activity of the sputum dialysates was significantly lower than that of the serum dialysate; this finding was correlated with greater binding by sputum. Thus, both binding and antagonism by ions evidently reduce the level of bioactivity of gentamicin in serum and in sputum. Purulent sputum, whether from children with cystic fibrosis or adults which bronchiectasis, is more inhibitory than serum; the greater degree of binding, rather than differences in the composition or quantity of cations, explains this difference.

We critically review formulas for temperature correction of pH, pCO2, and pO2 measurements in whole blood and the clinical usefulness of these formulas. We discuss both the theoretical derivation and experimental verification of temperature-induced changes. We recommend when to use and when not to use these formulas, based upon the clinical interpretation of these assays.

Intracellular free (cytosolic) calcium has been reported to be increased in the platelets of patients with essential hypertension. We investigated the possibility that the high cytosolic calcium concentration may be caused by a circulating plasma factor, by incubating platelets from normotensive subjects with plasma ultrafiltrates from patients with essential hypertension. The cytosolic calcium concentration in normal platelets increased after incubation with plasma from patients with untreated hypertension (80 +/- 15 percent [+/- SEM]) or from patients in whom hypertension was well controlled by calcium-influx blockers (129 +/- 33 percent). In contrast, the cytosolic calcium concentration was unchanged after incubation with plasma from normotensive subjects. When platelets from the patients were incubated with plasma from the controls, cytosolic calcium in platelets decreased by more than 30 percent, into the normal range (P less than 0.01). These data demonstrate that plasma from patients with essential hypertension contains a substance that increases the cytosolic calcium concentration in platelets. Cytosolic calcium is a trigger for vascular smooth-muscle-cell contraction, and if the plasma factor acts on these cells as it acts on platelets, it may be responsible for the increased peripheral vascular resistance associated with hypertension.